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Clark, Marcus Ramsay

One or more keywords matched the following properties of Clark, Marcus Ramsay

Property	Value
keywords	Developmental Biology
overview	Our laboratory has a long-standing interest in B cell antigen receptor (BCR) signaling and how BCR dependent processes regulate specific cell fate decisions. In the bone marrow, we have been working to understand how signals initiated through the pre-BCR, in conjunction with those delivered through the IL-7 receptor, coordinate cell cycle progression with immunoglobulin light chain gene recombination. These studies resulted in discovery of the epigenetic reader BRWD1 as critical for both regulating Ig-kappa accessibility and in coordinating broad transcriptional programs in early and late B lymphopoiesis. Recently, we have demonstrated that the pre-BCR initiates an IRF4-CXCR4 feedforward loop and that it is CXCR4 that directly signals Ig-kappa recombination. These latter findings fundamentally rewrite the canonical model of B lymphopoiesis. Furthermore, they are the first demonstration of a direct and independent role for CXCR4 in driving an important biological process. In the periphery, we have focused on the molecular control of germinal centers (GCs). Recently, we have recently defined two novel B cell populations within the dark zone that both allow compartmentalization of fundamental GC functions and reveal the molecular programs of the GC cycle. This new three population model fundamentally rewrites the GC paradigm. In all these areas, we have derived novel in vivo models, and have performed directed in vitro studies, to obtain definitive insights into these processes. Our translational studies have focused on how in situ adaptive immune responses drive tubulointerstitial inflammation in human lupus nephritis. For these studies, we have used deep machine learning to develop novel image analysis tools to quantify and identify functional relationships between different T cell and antigen presenting cell populations in situ. Remarkably, this bioinformatics platform approaches the sensitivity and specificity of two-photon excitation microscopy (TPEM). However, unlike TPEM, it can be applied to the study of human disease. We have also used single cell technologies to understand B cell selection at sites of inflammation and determine the interrelationships between transcriptional state and antigenic specificity.

Property

Value

keywords

Developmental Biology

overview

Our laboratory has a long-standing interest in B cell antigen receptor (BCR) signaling and how BCR dependent processes regulate specific cell fate decisions. In the bone marrow, we have been working to understand how signals initiated through the pre-BCR, in conjunction with those delivered through the IL-7 receptor, coordinate cell cycle progression with immunoglobulin light chain gene recombination. These studies resulted in discovery of the epigenetic reader BRWD1 as critical for both regulating Ig-kappa accessibility and in coordinating broad transcriptional programs in early and late B lymphopoiesis. Recently, we have demonstrated that the pre-BCR initiates an IRF4-CXCR4 feedforward loop and that it is CXCR4 that directly signals Ig-kappa recombination. These latter findings fundamentally rewrite the canonical model of B lymphopoiesis. Furthermore, they are the first demonstration of a direct and independent role for CXCR4 in driving an important biological process. In the periphery, we have focused on the molecular control of germinal centers (GCs). Recently, we have recently defined two novel B cell populations within the dark zone that both allow compartmentalization of fundamental GC functions and reveal the molecular programs of the GC cycle. This new three population model fundamentally rewrites the GC paradigm. In all these areas, we have derived novel in vivo models, and have performed directed in vitro studies, to obtain definitive insights into these processes. Our translational studies have focused on how in situ adaptive immune responses drive tubulointerstitial inflammation in human lupus nephritis. For these studies, we have used deep machine learning to develop novel image analysis tools to quantify and identify functional relationships between different T cell and antigen presenting cell populations in situ. Remarkably, this bioinformatics platform approaches the sensitivity and specificity of two-photon excitation microscopy (TPEM). However, unlike TPEM, it can be applied to the study of human disease. We have also used single cell technologies to understand B cell selection at sites of inflammation and determine the interrelationships between transcriptional state and antigenic specificity.

One or more keywords matched the following items that are connected to Clark, Marcus Ramsay

Item Type	Name
Concept	Actins
Concept	Adenosine
Concept	Antigen-Antibody Complex
Concept	Antigens, Ly
Concept	Adolescent
Concept	Adenosine Triphosphatases
Concept	Sodium-Potassium-Exchanging ATPase
Concept	Agammaglobulinemia
Concept	Bone Marrow Cells
Concept	Alleles
Concept	Amino Acid Sequence
Concept	Adult
Concept	Blood Proteins
Concept	Antibody Formation
Concept	Cell Communication
Concept	Animals
Concept	Hypoxia
Concept	Antibodies, Monoclonal
Concept	Anti-Inflammatory Agents
Concept	Histocompatibility Antigens Class II
Concept	B-Lymphocytes
Concept	Base Sequence
Concept	Cell Differentiation
Concept	Cell Movement
Concept	Cell Nucleus
Concept	Autoantigens
Concept	DNA Damage
Concept	Autoantibodies
Concept	Binding Sites
Concept	Biological Transport
Concept	Biopsy
Concept	Bone Marrow
Concept	Cell Membrane
Concept	Cell Division
Concept	Child
Concept	Cells
Concept	Clone Cells
Concept	Cell Cycle
Concept	Genes, Immunoglobulin
Concept	Cicatrix
Concept	Cross-Linking Reagents
Concept	DNA-Binding Proteins
Concept	Cytoplasm
Concept	Dendritic Cells
Concept	Immunoglobulin Constant Regions
Concept	Interleukin-2
Concept	Interleukins
Concept	Child, Preschool
Concept	Enzyme Precursors
Concept	Cross-Sectional Studies
Concept	Disease Susceptibility
Concept	Interferons
Concept	Endocytosis
Concept	Enzyme Activation
Concept	Methyltransferases
Concept	Gene Expression Regulation
Concept	Kidney Diseases
Concept	Killer Cells, Natural
Concept	Graft Rejection
Concept	T-Lymphocytes, Helper-Inducer
Concept	Hematopoietic Stem Cells
Concept	Immunoglobulin Heavy Chains
Concept	Enzyme-Linked Immunosorbent Assay
Concept	Flow Cytometry
Concept	Fluorescent Antibody Technique
Concept	Infant
Concept	Inflammation
Concept	Isoenzymes
Concept	Leukocytes, Mononuclear
Concept	Lupus Nephritis
Concept	Membrane Glycoproteins
Concept	Membrane Proteins
Concept	Immunoglobulin E
Concept	Models, Molecular
Concept	Phospholipids
Concept	Mammals
Concept	Mice, Transgenic
Concept	Immunoglobulin Variable Region
Concept	Immunohistochemistry
Concept	Molecular Sequence Data
Concept	Mice, Inbred BALB C
Concept	Mice, Inbred C57BL
Concept	Recombination, Genetic
Concept	Mutation
Concept	Myoglobin
Concept	Peptide Fragments
Concept	Kidney Tubules
Concept	Phagocytosis
Concept	Ligands
Concept	Liver
Concept	Mice, Inbred NZB
Concept	Phosphoproteins
Concept	Phosphorylation
Concept	Female
Concept	Plasma Cells
Concept	Protein-Tyrosine Kinases
Concept	Protein Binding
Concept	Proto-Oncogene Proteins
Concept	Proteins
Concept	Transcription Factors
Concept	Glycine
Concept	Immunoglobulin G
Concept	Image Processing, Computer-Assisted
Concept	Immunoglobulin Joining Region
Concept	Receptors, Antigen
Concept	Receptors, Antigen, B-Cell
Concept	Cohort Studies
Concept	Sodium
Concept	RNA
Concept	RNA Polymerase II
Concept	Mass Spectrometry
Concept	Histones
Concept	Humans
Concept	Cluster Analysis
Concept	Time Factors
Concept	Transcription, Genetic
Concept	Protein Biosynthesis
Concept	Immunoglobulin alpha-Chains
Concept	Immunoglobulin lambda-Chains
Concept	Genome
Concept	Monophenol Monooxygenase
Concept	United States
Concept	Immunoglobulin Class Switching
Concept	Kidney
Concept	Kidney Failure, Chronic
Concept	Kidney Glomerulus
Concept	Phosphotransferases (Alcohol Group Acceptor)
Concept	Histocompatibility Antigens Class I
Concept	Biomarkers
Concept	Lung
Concept	Male
Concept	Gene Rearrangement
Concept	Gene Rearrangement, T-Lymphocyte
Concept	Trans-Activators
Concept	Reverse Transcriptase Polymerase Chain Reaction
Concept	Tumor Cells, Cultured
Concept	Tyrosine
Concept	Valine
Concept	Electrophoretic Mobility Shift Assay
Concept	Up-Regulation
Concept	Kidney Transplantation
Concept	B-Lymphocyte Subsets
Concept	Antigens, CD
Concept	Lupus Erythematosus, Systemic
Concept	Microscopy
Concept	Gene Rearrangement, B-Lymphocyte, Light Chain
Concept	CD4-Positive T-Lymphocytes
Concept	Interleukin-7
Concept	Antibodies, Antiphospholipid
Concept	Proto-Oncogene Proteins c-myc
Concept	Mutagenesis, Site-Directed
Concept	Case-Control Studies
Concept	T-Lymphocyte Subsets
Concept	Microscopy, Immunoelectron
Concept	Sequence Analysis, DNA
Concept	Protein Structure, Tertiary
Concept	Methylation
Concept	Phosphatidylinositol Phosphates
Concept	Treatment Outcome
Concept	Nephritis, Interstitial
Concept	Genomic Instability
Concept	Severe Combined Immunodeficiency
Concept	RNA-Binding Proteins
Concept	Point Mutation
Concept	Antigen Presentation
Concept	Apoptosis
Concept	Mice, Knockout
Concept	CD8-Positive T-Lymphocytes
Concept	Cell Proliferation
Concept	Inflammation Mediators
Concept	Phosphotyrosine
Concept	ras Proteins
Concept	Apoptosis Regulatory Proteins
Concept	Th2 Cells
Concept	Models, Immunological
Concept	Proto-Oncogene Proteins c-vav
Concept	Gene Regulatory Networks
Concept	MAP Kinase Kinase Kinases
Concept	Receptors, CXCR4
Concept	Protein Transport
Concept	Calcium Signaling
Concept	Chemokine CXCL12
Concept	Lymphocyte Count
Concept	src Homology Domains
Concept	Inflammasomes
Concept	Single-Cell Analysis
Concept	Primary Cell Culture
Concept	Proteomics
Concept	Chromatin Assembly and Disassembly
Concept	Cyclin-Dependent Kinase 4
Concept	Microarray Analysis
Concept	Proto-Oncogene Proteins c-bcl-2
Concept	COS Cells
Concept	Microscopy, Confocal
Concept	Cyclin-Dependent Kinase Inhibitor p16
Concept	Cell Cycle Proteins
Concept	Oligonucleotide Array Sequence Analysis
Concept	Amino Acid Motifs
Concept	Active Transport, Cell Nucleus
Concept	Receptors, Interleukin-7
Concept	Proteome
Concept	Dendritic Cells, Follicular
Concept	Gene Expression Profiling
Concept	STAT3 Transcription Factor
Concept	Phagosomes
Concept	Type C Phospholipases
Concept	Promoter Regions, Genetic
Concept	Mice
Concept	Endosomes
Concept	Severity of Illness Index
Concept	RNA, Messenger
Concept	Immunoglobulin Light Chains, Surrogate
Concept	Sulfonamides
Concept	Ubiquitin-Protein Ligases
Concept	Immunity, Humoral
Concept	Interferon Regulatory Factors
Concept	BH3 Interacting Domain Death Agonist Protein
Concept	Palatine Tonsil
Concept	PAX5 Transcription Factor
Concept	Cyclin D3
Concept	Laser Capture Microdissection
Concept	Immunoprecipitation
Concept	Spleen
Concept	Adaptor Proteins, Signal Transducing
Concept	Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Concept	Precursor Cells, B-Lymphoid
Concept	Immunoblotting
Concept	Down-Regulation
Concept	Autoimmunity
Concept	Histone Acetyltransferases
Concept	Cyclins
Concept	Cell Death
Concept	Phosphatidylinositol 3-Kinase
Concept	CD79 Antigens
Concept	Polymerase Chain Reaction
Concept	Genes, p53
Concept	Retinoblastoma Protein
Concept	Proliferating Cell Nuclear Antigen
Concept	Pre-B Cell Receptors
Concept	Gene Silencing
Concept	Imaging, Three-Dimensional
Concept	Gene Targeting
Concept	Homeodomain Proteins
Concept	Ubiquitin
Concept	Germinal Center
Concept	Cell Lineage
Concept	Phosphatidylinositol 3-Kinases
Concept	Lymphopoiesis
Concept	JNK Mitogen-Activated Protein Kinases
Concept	Extracellular Signal-Regulated MAP Kinases
Concept	T-Lymphocytes, Regulatory
Concept	STAT5 Transcription Factor
Concept	GRB2 Adaptor Protein
Concept	Basic Helix-Loop-Helix Transcription Factors
Concept	Cell Cycle Checkpoints
Concept	Transcriptome
Concept	Adaptive Immunity
Concept	RNA, Small Interfering
Concept	Microscopy, Fluorescence, Multiphoton
Concept	V(D)J Recombination
Concept	Cellular Microenvironment
Concept	Cell Line, Tumor
Concept	Intracellular Signaling Peptides and Proteins
Concept	Cell Size
Concept	Cyclin-Dependent Kinase Inhibitor p27
Concept	Toll-Like Receptors
Concept	Toll-Like Receptor 9
Concept	Cyclin-Dependent Kinase 6
Concept	Ikaros Transcription Factor
Concept	Forkhead Transcription Factors
Concept	Receptor, Notch1
Concept	Phospholipase C gamma
Concept	Lymphoid Progenitor Cells
Concept	Cyclin D2
Concept	Allergens
Concept	Antibodies, Antinuclear
Concept	Artificial Intelligence
Concept	Binding, Competitive
Concept	Calcium
Concept	Carrier Proteins
Concept	Cell Line
Concept	Cell Survival
Concept	Cells, Cultured
Concept	Chromatin
Concept	Crosses, Genetic
Concept	Enhancer Elements, Genetic
Concept	Follow-Up Studies
Concept	Immunoglobulins
Concept	Immunoglobulin kappa-Chains
Concept	Immunoglobulin Light Chains
Concept	Immunologic Memory
Concept	Lymphocyte Activation
Concept	Lymphocytes
Concept	Mice, Mutant Strains
Concept	Microscopy, Fluorescence
Concept	Models, Biological
Concept	Nuclear Proteins
Concept	Organ Specificity
Concept	Phenotype
Concept	Predictive Value of Tests
Concept	Histone-Lysine N-Methyltransferase
Concept	Receptors, Antigen, T-Cell
Concept	Recombinant Fusion Proteins
Concept	Staining and Labeling
Concept	T-Lymphocytes
Concept	Translocation, Genetic
Concept	Transplantation, Homologous
Concept	Vimentin
Concept	Signal Transduction
Concept	Transcriptional Activation
Concept	Tumor Suppressor Protein p53
Concept	Cytokines
Concept	Mice, SCID
Concept	Mice, Inbred NOD
Concept	Sequence Analysis, RNA
Concept	Receptors, Platelet-Derived Growth Factor
Concept	Clonal Anergy
Concept	DNA Primers
Concept	Bridged Bicyclo Compounds, Heterocyclic
Concept	Computational Biology
Concept	Receptor, Platelet-Derived Growth Factor beta
Concept	Genomics
Concept	Quantitative Trait Loci
Concept	Epigenesis, Genetic
Concept	Macromolecular Substances
Concept	Proto-Oncogene Proteins c-akt
Concept	Proto-Oncogene Proteins c-bcl-6
Concept	Ubiquitination
Concept	Young Adult
Academic Article	The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways.
Academic Article	Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha.
Academic Article	A point mutation in the constant region of Ig lambda1 prevents normal B cell development due to defective BCR signaling.
Academic Article	Selection of B lymphocytes in the periphery is determined by the functional capacity of the B cell antigen receptor.
Academic Article	B cell antigen receptor signaling and internalization are mutually exclusive events.
Academic Article	HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse.
Academic Article	In situ B cell-mediated immune responses and tubulointerstitial inflammation in human lupus nephritis.
Academic Article	Subnuclear cyclin D3 compartments and the coordinated regulation of proliferation and immunoglobulin variable gene repression.
Academic Article	Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.
Academic Article	Regulation of lymphocyte progenitor survival by the proapoptotic activities of Bim and Bid.
Academic Article	A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation.
Academic Article	A unique function for cyclin D3 in early B cell development.
Academic Article	Ubiquitinylation of Ig beta dictates the endocytic fate of the B cell antigen receptor.
Academic Article	Endocytic sequestration of the B cell antigen receptor and toll-like receptor 9 in anergic cells.
Academic Article	Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development.
Academic Article	Ikaros and Aiolos inhibit pre-B-cell proliferation by directly suppressing c-Myc expression.
Academic Article	Predicting outcomes of lupus nephritis with tubulointerstitial inflammation and scarring.
Academic Article	Ig alpha and Ig beta are required for efficient trafficking to late endosomes and to enhance antigen presentation.
Academic Article	The pre-B cell receptor in B cell development: recent advances, persistent questions and conserved mechanisms.
Academic Article	PU.1 and Spi-B are required for normal B cell receptor-mediated signal transduction.
Academic Article	Cell distance mapping identifies functional T follicular helper cells in inflamed human renal tissue.
Academic Article	Vimentin is a dominant target of in situ humoral immunity in human lupus tubulointerstitial nephritis.
Academic Article	The emerging role of the inflammasome in kidney diseases.
Academic Article	Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling.
Academic Article	Balancing Proliferation with Ig? Recombination during B-lymphopoiesis.
Academic Article	RAG Represents a Widespread Threat to the Lymphocyte Genome.
Academic Article	Histone reader BRWD1 targets and restricts recombination to the Igk locus.
Academic Article	Self-reactive IgE exacerbates interferon responses associated with autoimmunity.
Academic Article	EZH2 Regulates the Developmental Timing of Effectors of the Pre-Antigen Receptor Checkpoints.
Academic Article	BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis.
Academic Article	Igß ubiquitination activates PI3K signals required for endosomal sorting.
Academic Article	Regulated Capture of V? Gene Topologically Associating Domains by Transcription Factories.
Academic Article	Quantifying in situ adaptive immune cell cognate interactions in humans.
Academic Article	Transcription factories in Ig? allelic choice and diversity.
Academic Article	CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis.
Academic Article	B-1a cells acquire their unique characteristics by bypassing the pre-BCR selection stage.
Academic Article	Kidney tissue hypoxia dictates T cell-mediated injury in murine lupus nephritis.
Academic Article	Control of Early B Cell Development by the RNA N6-Methyladenosine Methylation.
Academic Article	Machine Learning to Quantify In Situ Humoral Selection in Human Lupus Tubulointerstitial Inflammation.
Academic Article	Quantifying the effects of biopsy fixation and staining panel design on automatic instance segmentation of immune cells in human lupus nephritis.
Academic Article	Compartments and Connections Within the Germinal Center.
Academic Article	Artificial Intelligence and Cellular Segmentation in Tissue Microscopy Images.
Academic Article	Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection.
Academic Article	Asymmetrical forward and reverse developmental trajectories determine molecular programs of B cell antigen receptor editing.
Academic Article	IRF4 expression by lung dendritic cells drives acute but not Trm cell-dependent memory Th2 responses.
Academic Article	The endogenous repertoire harbors self-reactive CD4+ T cell clones that adopt a follicular helper T cell-like phenotype at steady state.
Concept	Cell Plasticity
Concept	Machine Learning
Concept	Forkhead Box Protein O1
Concept	Enhancer of Zeste Homolog 2 Protein
Concept	NLR Family, Pyrin Domain-Containing 3 Protein
Concept	Forkhead Box Protein O3
Concept	Bcl-2-Like Protein 11
Concept	Syk Kinase
Concept	CCCTC-Binding Factor
Concept	Gene Ontology
Concept	Polycomb Repressive Complex 2
Concept	Ataxia Telangiectasia Mutated Proteins
Concept	Myeloid Cell Leukemia Sequence 1 Protein
Concept	Allografts
Academic Article	Antigenic responses are hallmarks of fibrotic interstitial lung diseases independent of underlying etiologies.
Academic Article	Molecular mechanisms insulating proliferation from genotoxic stress in B lymphocytes.
Academic Article	Lineage-specific 3D genome organization is assembled at multiple scales by IKAROS.
Academic Article	BRWD1 orchestrates small pre-B?cell chromatin topology by converting static to dynamic cohesin.
Academic Article	Pseudo-spectral angle mapping for automated pixel-level analysis of highly multiplexed tissue image data.

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